Multiple circulating wavefronts in an excitable medium produced by computer simulations are an example of spatio-temporal chaos. Their close similarity to experimentally-recorded activation patterns during atrial or ventricular fibrillation suggest that fibrillation may also be a form of spatio-temporal chaos, and raises the possibility that recently-developed chaos control strategies can be applied to fibrillation. We have previously shown that a pacing algorithm based on chaos control theory could successfully regularize a chaotic ventricular tachycardia induced by ouabain in isolated rabbit ventricle. The major objective of this project is to determine whether a similar strategy can be developed for ventricular fibrillation. We have modified the van Capelle & Durrer computer model of propagation in a two-dimensional excitable lattice, and have shown that multiple circulating wavefronts (spiral waves) simulating fibrillation can be induced. Local site recordings show clear evidence of chaotic behavior, and exhibit the dynamic features (fixed point and stable and unstable manifolds) necessary to apply the OGY chaos control method, which we successfully applied to the chaotic ouabain-induced arrhythmia. The model closely simulates the behavior of circulating reentrant wavefronts in the in vitro canine epicardial slice preparation described in Project 2, which also shows evidence of chaos at local recording sites. Criteria for detecting spatio-temporal chaos at individual elements in the lattice (equivalent to the information that could be obtained from a local intracardiac electrogram) will be developed in the van Capelle & Durrer model, and this information used develop a perturbation strategy based on chaos control theory (analogous to pacing at a one or more sites in the lattice) to determine whether local and global chaos control can be achieved. The results of computer simulations will be directly validated experimentally using the in vitro canine epicardial slice preparation and, if successful, adapted to the in vivo fibrillating canine heart. A second objective of the project is to further understand and improve the chaos control pacing algorithm which we have previously successfully applied to ouabain-induced ventricular tachycardia in the rabbit interventricular septum, a less spatially complex chaotic cardiac arrhythmia. Using high resolution activation mapping with extracellular electrodes, the ouabain-induced arrhythmia will be mapped to evaluate its mechanism and spatial properties, and to gain insight into the mechanism by which the chaos control pacing algorithm is effective. Improvements to our current chaos control algorithm will be further developed and tested in the septal preparation. These improvements to the chaos control pacing algorithm in the ouabain-induced arrhythmia will be essential for chaos control pacing algorithms designed for fibrillation. Ultimately, the goal is to develop an intelligent pacing strategy based on chaos control theory which will either terminate fibrillation or significantly decrease the defibrillation threshold.